1-32695311-G-T

Variant names:

• chr1-32695311-G-T
• rs41265855
• NM_030786.3:c.787C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030786.3(SYNC):​c.787C>A​(p.Arg263Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R263C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYNC NM_030786.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61

Genes affected

SYNC (HGNC:28897): (syncoilin, intermediate filament protein) This gene encodes a member of the intermediate filament family which contains an N-terminal head domain, followed by a central coiled-coil region and a short C-terminal tail. The protein is highly expressed in skeletal and cardiac muscle. The protein links the dystrophin associated protein complex (DAPC) to desmin filaments in muscle and may have a structural role in striated muscle. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNC	NM_030786.3	c.787C>A	p.Arg263Ser	missense_variant	Exon 2 of 5	ENST00000409190.8	NP_110413.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNC	ENST00000409190.8	c.787C>A	p.Arg263Ser	missense_variant	Exon 2 of 5	2	NM_030786.3	ENSP00000386439.3
SYNC	ENST00000373484.4	c.787C>A	p.Arg263Ser	missense_variant	Exon 2 of 4	2		ENSP00000362583.3

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399670 Hom.: 0 Cov.: 98 AF XY: 0.00 AC XY: 0 AN XY: 690346

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Benign	0.55	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.56
Sift	Benign	0.049	D;T
Sift4G	Benign	0.20	T;T
Polyphen		0.96	P;P
Vest4		0.53
MutPred		0.63		Loss of catalytic residue at R263 (P = 0.1221);Loss of catalytic residue at R263 (P = 0.1221);
MVP		0.61
MPC		1.1
ClinPred		0.79	D
GERP RS		4.5
Varity_R		0.33
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41265855; hg19: chr1-33160912;